Hematology

ISSN: 1024-5332 (Print) 1607-8454 (Online) Journal homepage: http://www.tandfonline.com/loi/yhem20

Tuberculosis in acute leukemia: A clinico-

hematological profile

Pravas Mishra, Rajat Kumar, Manoranjan Mahapatra, Sanjay Sharma, Ashish

Dixit, Tathagat Chaterjee, D. R. Choudhry, Renu Saxena & V. P. Choudhry

To cite this article: Pravas Mishra, Rajat Kumar, Manoranjan Mahapatra, Sanjay Sharma,
Ashish Dixit, Tathagat Chaterjee, D. R. Choudhry, Renu Saxena & V. P. Choudhry (2006)
Tuberculosis in acute leukemia: A clinico-hematological profile, Hematology, 11:5-6, 335-340

To link to this article: http://dx.doi.org/10.1080/10245330600915818

Published online: 04 Sep 2013.

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 Hematology, October/December 2006; 11(5/6): 335-340 informa
healthcare

Tuberculosis in acute leukemia: A clinico-hematological profile

PRAVASMISHRA1, RAJAT KUMAR1, MANORANJAN MAHAPATRA1, SANJAY SHARMA2,

ASHISH DIXIT1, TATHAGAT CHATERJEE1, D. R. CHOUDHRyl, RENU SAXENA1, &
v. P. CHOUDHRyl

1Department of Hematology, AIIMS, New Delhi, India, and 2Department of Radiology, AIIMS, New Delhl~ India
Downloaded by [University of California, San Diego] at 10:02 01 March 2016

(Received 12 June 2006; accepted 19 July 2006)

Abstract
We studied 130 consecutive cases of acute leukemia over a 2-year period and identified 9 cases (6.9%) with active tuberculosis
(TB). Eight patients with TB had acute myeloid leukemia (AML). Patients with AML were more likely to develop TB as
compared to patients with acute lymphoblastic leukemia (ALL) despite the wider use of steroids and radiotherapy in ALL
protocols {OR 4.41 (el 0.53-36.44)}. Only 1 patient died of disseminated TB during post induction neutropenia. All other
patients were successfully managed using current anti-tuberculous therapy (ATT). On the whole, TB did not cause any undue
delay in chemotherapy and did not flare up during subsequent chemotherapy cycles. However it is not a commonly described
infection in acute leukemia and a high index of suspicion is warranted especially in areas endemic for TB.

Keywords: Acute leukemia, tuberculosis, neutropenia, cell-mediated immunity

Introduction leukemia, or within 6 months after completion of

treatment for acute leukemia.
The predisposition of patients with acute leukemia
Out of 130 acute leukemia patients (86 acute
to infections is well known [1,2]. Host defenses
myeloid leukemia (AML) and 44 acute lymphoid
including cell-mediated immunity are low in cases of
leukemia (ALL)), 9 patients were identified to have
acute leukemia due to disease or secondary to
TB. Radiological features, Ziehl-Neelsen staining for
therapy. These infections are mainly bacterial and
acid-fast bacilli (AFB), culture, polymerase chain
fungal. Tuberculosis (TB) has not been a common
reaction analysis (peR) and response to treatment
infection in most series. TB in acute leukemia might
were taken into consideration while diagnosing TB.
have been underestimated, due to use of drugs like
Response to anti-tuberculous treatment was defined
amikacin and quinolones that are also effective
when patients became afebrile and the lesions
against TB. We present retrospective data on TB in
subsided. Presence of AFB on Ziehl-Neelsen staining
acute leukemia patients admitted for therapy in our
and culture was taken as definitive evidence of TB
department.
whereas radiological data and a response to treatment
were taken as possible evidence for TB.
Material and methods TB was managed with four drugs (rifampicin
10mg/m2, isoniazid 5 mg/m2, pyrazinamide 30 mg/m2
Data on acute leukemia patients admitted in the
and ethambutol 20 mg/m2).
hematology department from January 2003 to
December 2004 was analysed. Patients who were
diagnosed to have TB were identified. TB was
Results
considered to be associated with acute leukemia if it
was diagnosed 6 months before diagnosis of acute The clinical and laboratory features of our cases are
leukemia, concomitantly or during treatment of acute summarized in Table I.

Correspondence: P. Mishra, Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
E-mail: pravas_mishra@rediffmail.com

ISSN 1024-5332 printiISSN 1607-8454 online © 2006 Informa UK Ltd.

DOl: 10.1080/10245330600915818
Downloaded by [University of California, San Diego] at 10:02 01 March 2016

336
P Mishra et al.

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Of the 9 patients with TB, 8 had AML and 1 had
ALL. Thus patients with AML were more likely to
develop TB disease {OR 4.41 (CI 0.53-36.44)}.
There were 8 males. Four cases (cases 1-4) were
diagnosed to have TB after induction therapy. All 4
patients had recovered their neutrophil counts by day
30 post chemotherapy. Cases 1-4 were in remission at
the time of diagnosis of TB. Case 3 developed a
pyopneumothorax after induction. Her symptoms and
general condition improved after the start of anti-
tuberculous therapy (ATT). Chest lesions resolved
with lung expansion and drying of fluid. She received
two further consolidations with high dose cytosine
arabinoside, but died of an Escherichia coli sepsis
(blood culture positive) during neutropenia following
the third consolidation. Case 5 continued to have fever
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in spite of improving neutrophil counts and developed
ascites, which showed AFB. He did not respond to
ATTand died.
Two patients (cases 6,7) had TB before diagnosis of
acute leukemia. These cases were found to have acute
leukemia within 2 months of diagnosis of TB. At the
time of diagnosis ofTB, neither case had any evidence
of acute leukemia on peripheral smear.
One patient (case 8) was diagnosed concurrently
with acute leukemia. He received chemotherapy after
resolution of chest and abdominal lesions.
The last case of acute promyelocytic leukemia
(APML) developed a chest wall abscess 2 months after
completion of maintenance therapy with mercapto-
purine, methotrexate and tretinoin. Pus from the
abscess stained for AFB.
None of the patients were neutropenic at the time of
diagnosis of TB. No patient had a past history of TB
and all were human immunodeficiency virus negative.
N one of the cases had evidence of any other infection
after detailed investigations.
Discussion
TB infection is acquired by inhalation of infectious
droplet nuclei. It is estimated that 10% of infected
persons eventually develop active TB. The average
prevalence of all forms of TB in the general Indian
population is 5/1000 [3], with a 1.5% annual risk
of acquiring TB infection [4]. TB disease is the result
of reactivation of endogenous infection. The risk of
developing disease after being infected depends on
endogenous factors such as the patients' innate
immunity and defects in cell mediated immunity.
Thus it is possible that patients with acute leukemia
are at a higher risk of developing TB.
The estimated prevalence in acute leukemia varies
from 3 to 4/1000 new cases of acute leukemia in
western literature [5,6] to 22-28/1000 new cases
in Indian data [1,2,7,8]. In our study population TB
was seen in 6.9% of the cases, a prevalence of69/1000
new cases. We have a higher prevalence as compared
Tuberculosis in acute leukemia 337
to western data on account of the higher prevalence of
TB in the general Indian population.
The previously reported cases of acute leukemia are
summarized in Table II. Forty nine cases including the
9 cases in our study were identified. This includes 6
cases of atypical mycobacteria. There were 25 AML and
13 ALL patients. Information regarding type of acute
leukemia in the other 11 was lacking. It is interesting to
note that the three Indian series had exactly two cases
each. Our study covers a broader period than the other
Indian studies which confined themselves to the
neutropenic period or autopsy findings.
TB can present in any site and cases of disseminated
TB with hepatosplenic involvement can be confused
with candida [11]. Thus an aspirate/biopsy of the
target lesion showing granulomas, AFB or a positive
culture for mycobacteria is essential to differentiate
mycobacterial infection from other infections.
It was suggested that intensity of treatment
increases the likelihood ofTB especially, with addition
of radiotherapy and steroids [5]. Treatment with
steroids and other immunosuppressive therapies, like
methotrexate result in defective cell mediated immu-
nity. Therefore an increased prevalence of TB would
be expected in ALL. However, our own cases and the
review of literature show a predilection for AML,
a group of patients less likely to receive steroids or
radiotherapy. The reason for AML preponderance is
not clear and could reflect monocyte/macrophage
dysfunction.
There have been few studies on the association of
mycobacteria with acute leukemia patients treated
with conventional chemotherapy. They have been
mostly reported in isolation or as part of general
studies on infection in acute leukemia. On the other
hand there have been several studies on mycobacteria,
including atypical mycobacteria, in stem cell trans-
plant patients [22-27]. In these patients, total body
irradiation, chronic graft versus host disease, and
underlying lung disease (chronic pulmonary disease,
bronchiolitis obliterans) have been identified as risk
factors for both typical and atypical mycobacterial
infection [22-27]. These patients were estimated to
be twice at risk for developing TB disease as compared
to the general population even in endemic areas [24].
Even so, the risk is lower than solid organ transplant
and AIDS patients, who have lifelong and more
intense immunosupression [24]. We have studied only
those patients with acute leukemia, who have received
conventional chemotherapy alone.
TB has been associated with a very high mortality
(33-100%) in other hematological malignancies like
Hodgkin's disease, chronic myelogenous leukemia
and multiple myeloma [5], but usually follows a
benign course in acute leukemia with a good
response to anti-tuberculous treatment. Except for
case 5 in our series, TB did not have any adverse
outcome post-induction in the remaining cases.
 338 P Mishra et al.

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Cases 1-3 recovered from neutropenia even in the
absence of definitive treatment for TB. In case 3,
there was no evidence to suggest a flare-up of her
old lesions at the time of death. There was no flare-
up of old lesions with the appearance of leukemia, or
during subsequent chemotherapy in the remaining
cases. About 17 of the 38 patients in literature
received definitive treatment for TB and 15
responded (Table II). In six of the cases in literature
where information was available, TB did not prolong
the neutropenia after chemotherapy, with counts
recovering by day 30 [9-11].
We did not specifically culture for atypical
mycobacteria. This is important because INH has
little role in atypical mycobacteria where macrolides
like clarithromycin, azithromycin are used in combi-
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nation with other anti-tuberculous drugs like rifampi-
cin and ethambutol [28]. Atypical mycobacteria are
ubiquitous organisms. Clinical presentation alone
cannot differentiate atypical mycobacteria from
tuberculous mycobacteria. Stringent diagnostic cri-
teria necessitate the presence of positive culture from
target lesion as well as concomitant blood culture/or
histological evidence of tissue invasion for definite
diagnosis of atypical mycobacteria [26].
An earlier study on TB in Indian BMT patients
suggested that all cases with AFB positivity should be
considered tuberculous, as the prevalence of TB is
high in India [25]. However another center from India
has reported cases of atypical mycobacteria [29]. A
study from Hong Kong [27] found equal prevalence of
tuberculous and non-tuberculous mycobacteria in
their post-BMT patients. Thus we should maintain a
high index of suspicion for atypical mycobacteria in
Indian patients as well.
Conclusion
There is a high association of TB in our cases of acute
leukemia. This has been predominantly seen in AML.
Immunosupression as a result of malignancy or
subsequent chemotherapy might predispose to acti-
vation of TB disease in our patients who already come
from an endemic area. A high index of suspicion is
required to diagnose TB in cases of acute leukemia. If
detected early, TB responds readily to therapy with
appropriate drugs and does not appear to have an
adverse outcome on acute leukemia management.
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